PROJECT SUMMARY/ABSTRACT Humans have a remarkable capacity to adapt to changing circumstances and learn new information from feedback in the environment. Failures to use feedback to adapt or maintain behavior are implicated in a wide variety of brain disorders, including schizophrenia 1, addiction 2, autism 3, Parkinson's disease 4,5, Tourette syndrome 6, and attention deficit hyperactive disorder 6. A better understanding of the neural mechanisms underlying feedback processing and learning has the potential to bridge neuroscience research across a range of species and theoretical and methodological frameworks, and to help gain insight into brain disorders. This project examines the mechanisms of positive and negative feedback-guided learning in healthy humans from a physiologically inspired perspective centered on large-scale brain networks and how they interact through synchronized electrophysiological rhythms 7,8. We focus on rhythms hypothesized to index frontal cortical mechanisms that compute and communicate the need for adjustment or maintenance of current information processing across broad networks during learning. We combine high-density electroencephalographic (EEG) measurements of synchronized rhythms with high definition transcranial direct-current stimulation (HD-tDCS) 9,10 to determine whether it is possible to modify components of frontal activity and cause bi-directional changes in next-trial behavior and learning success. Our preliminary data are highly encouraging and indicate that we can causally manipulate the timing of low-frequency rhythmic activity, and improve or impair learning measured behaviorally. The goals of the research program are to use novel neuroscience tools and analysis procedures to gain a deeper understanding of the cognitive mechanisms underlying the flexible adjustment of behavior and learning, and contribute new knowledge to the development of effective, non-pharmacological interventions for improving cognition in healthy and patient populations.